Molecular cloning studies have identified four glutamate receptor (gluR) subunits which, when expressed together, account for many of the functional properties observed in native ionotropic non-NMDA receptors. The cDNA for one subunit, gluR-2, when expressed with the other gluR subunits, dominates the electrophysiological properties and confers ionic selectivity, making the channels impermeant to Ca++. A single arginine residue in transmembrane domain II of gluR-2 controls the ion selectivity. Interestingly, while the cDNA for gluR-2 encodes this arginine, the gluR-2 gene codes for glutamine at this position. This single nucleotide difference results from RNA editing. The specific aim of this proposal is to understand RNA editing and its role in glutamate receptor activity. Thus, the overall goal of these studies is to further our understanding of a newly identified mechanism of gene regulation, and to increase our understanding of neuro- transmission in the central nervous system.